Display options
Share it on

Int J Clin Pharmacol Toxicol. 2017;6(1):242-249. Epub 2017 Jan 03.

CYP2B6 Genotype Guided Dosing of Propofol Anesthesia in the Elderly based on Nonparametric Population Pharmacokinetic Modeling and Simulations.

International journal of clinical pharmacology & toxicology

Andy R Eugene

Affiliations

  1. Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental, Therapeutics, Gonda 19, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

PMID: 28154789 PMCID: PMC5282793

Abstract

OBJECTIVE: The primary aim of this article is to test the hypothesis that nonparametric pharmacometric modeling will accurately identify CYP2B6 genotype subgroups based on data from a study that reported results based on parametric pharmacokinetics (PK).

METHODS: Propofol concentration-time data were originally reported in the Kansaku et al. 2011 publication. Nonparametric Nonlinear Mixed Effects Modeling (NLME) was conducted using the PMETRICS R package while population pharmacokinetic model parameters were estimated using a FORTRAN compiler. Finally, model-based dosing simulations were conducted in the MATLAB Simbiology.

RESULTS: A total of 51 patients were included in the final PK analysis. A two-compartment gamma multiplicative error model adequately described the propofol concentration-time data. The precision of the goodness-of-fit plots resulted in an R

CONCLUSION: Based on the pharmacometric modeling and simulation, if no dosage adjustments are made for the elderly CYP2B6 AA and AG genotypes, a 250% higher propofol blood exposure will be evident within 1-hour from the start of the infusion. Thus, based on the pharmacokinetic model, genotyping elderly patients for the CYP2B6 AA and AG gene variants will decrease the total propofol blood exposure during anesthesia and sedation when an infusion dose adjustment is made to 25mg/kg/min.

Keywords: anesthesia; genotype; nonparametric pharmacokinetics; precision medicine; propofol

Conflict of interest statement

The author declares no conflict of interests.

References

  1. Anesthesiology. 2001 Jan;94(1):110-9 - PubMed
  2. Eur J Clin Pharmacol. 2012 Apr;68(4):397-406 - PubMed
  3. Eur J Clin Pharmacol. 2002 Sep;58(6):417-21 - PubMed
  4. Anesthesiology. 2000 Mar;92(3):727-38 - PubMed
  5. CPT Pharmacometrics Syst Pharmacol. 2012 Sep 26;1:e6 - PubMed
  6. J Appl Genet. 2016 Nov 8;:null - PubMed
  7. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4 - PubMed
  8. Front Genet. 2013 Mar 05;4:24 - PubMed
  9. A A Case Rep. 2016 Dec 1;7(11):243-246 - PubMed
  10. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):131-6 - PubMed
  11. N Engl J Med. 2015 Feb 26;372(9):793-5 - PubMed
  12. Biol Pharm Bull. 2015;38(4):531-5 - PubMed
  13. Drug Metab Pharmacokinet. 2011;26(5):532-7 - PubMed
  14. Drug Metab Pharmacokinet. 2014;29(2):215-8 - PubMed
  15. Basic Clin Pharmacol Toxicol. 2013 Aug;113(2):126-31 - PubMed
  16. Ther Drug Monit. 2012 Aug;34(4):467-76 - PubMed
  17. Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):511-5 - PubMed
  18. Clin Ther. 2015 Dec 1;37(12):2676-85 - PubMed
  19. Anticancer Drugs. 2007 Feb;18(2):111-26 - PubMed

Publication Types

Grant support